Microsatellite Instability of Circadian Clock Genes in Oral Squamous Cell Carcinoma and Efficacy of Anti-Tumour Drugs

Background: Circadian system coordinated and regulated multiple cellular procedures which implicating in cancer development such as metabolism, cell cycle and DNA damage response. Many studies suggested that clock genes contribute to the regulation of not only circadian rhythm, but also the regulation of apoptosis induced by anti-tumour drugs. In this study 13 Microsatellite markers of Circadian-Clock Genes were examined in 150 OSCC patients treated with cisplatin + 5FU (Arm-I) and Cisplatin + capecitabin ( Arm-II) to establish genetic marker for early detection as well as the marker responsible for drugs sensitivity and resistance for accurate clinical practice. Results: Overall incidence of LOH/MSI was 49%±18.84 with the frequency of LOH and MSI of individual markers ranged from 12-71%. LOH was relatively more frequently detected at five loci, namely Bmal-1 (42%), Per-1 (46%), Per-2(49%), rorβ (58%), c-fos (49%), whereas the MIS of above five markers were 53%, 65%, 69%, 63% and 71% respectively. Low incidence of MSI was observed in Clock-5 (16%), Rorα (12%) and E4BP4 (17%). Conclusion: The results of this study suggested that the microsatellites of Clock genes particularly Bmal-1, per-2, Rorβ and C-fos may be used as a marker to determine clinical staging, to evaluate the metastatic risk of OSCC, and as a novel target for the prevention and treatment of OSCC.